Endothelial health and endothelial damage are major concerns in regard to coronary bypass grafts. This is especially true in regard to the late patency of such grafted vessels. To date, saline has been frequently utilized as preservative fluid for harvested vessels intended for use in bypass surgery. However, it is well known that saline produces significant endothelial damage in such vessels. It follows, as has been noted in various studies, that saline preserved grafts suffer significant impairment of vessel structure and function after anastomosis. In part, such degradation can be related to the absence of blood constituents which, in combination with natural blood flow, are required to maintain endothelial health.
The endothelial lining of arterial walls produces what was once known as endothelium-derived relaxing factor (which has since been identified as nitric oxide). Nitric oxide is, in turn, required in order for acetylcholine to effect relaxation of arterial smooth muscle—and to avoid damaging vessel spasms/contractions often noted in excised grafts. NO, derived from the endothelium has further vessel patency functions beyond muscle relaxation. It is known to protect the vessel by inhibiting platelet and neutrophil adhesion to the endothelial walls as well as the arrest of smooth muscle cell proliferation. Based on the two aforementioned functions of NO, it follows that, in regard to maintaining patency of grafted vessels, preservation of the endothelium's natural production and release of NO is of extreme importance.
While, as discussed above, it is known that saline is a rather poor solution for use in preserving arterial grafts, blood is an excellent preservative. However, due to the fact that the normal constituents of blood (platelets, fibrin, leukocytes) as well as plasma components (such as cholesterol and triglycerides), negatively interact and damage endothelium during the harvesting/handling procedures, the simple infusion of blood into a harvested vessel would, of course, include additional draw backs. These interactions, of course, constitute an additional concern in regard to vessel patency. The aforementioned interactions of blood and plasma constituents with the endothelial lining are exacerbated in regard to blood which is allowed to pool. However, blood flowing through a vessel, as it does in its natural, pre-excised demonstrates greatly diminished interactions between the above-described blood/plasma constituents and the endothelial wall. More specifically, there is a substantially higher degree of interaction between blood/plasma components and the endothelial lining of vessels in stagnant blood, allowed to simply pool in an excised vessel, as opposed to the degree of interaction found in vessels conducting pulsatile, flowing blood.
In regard to blood flow and its effect upon harvested vessels beyond the aforementioned constituent/endothelial interactions, it is well known, that application of a pulsatile flow to preservative solutions will improve and help maintain vessel dilatation. Pulsatile solution flow is also known to improve, nitric oxide production and release. In addition, flow pulsatility is known to reduce harvested vessel spasm. More specifically, harvested vessels, “acclimated” or conditioned to pulsatility—prior to being placed into arterial circulation—have increased likelihood of maintaining post-graft viability.
In addition to preservative fluid composition and flow, the temperature of storage and/or preservative solutions utilized to maintain harvested vessel vitality is of great significance. More specifically, as fluid temperature decreases below normal body temperature, loss of endothelium increases. Fluid temperatures beyond normal body temperature can also be quite damaging. It would therefore seem that a superior preservative technique, especially useful for the preservation of harvested blood vessels, would include the use of solutions maintained at normal body temperature.
Harvested vessels are also highly susceptible to damage caused by exposure to improper pH. For example, the relative acidic nature of normal saline is known to have detrimental effects on the endothelium. Also, hypoxic conditions which effect harvested vessels removed from active circulation can also cause enough damage as to substantially reduce graft survival. In addition, maintaining the natural patency of the lumen of harvested vessels, once removed from circulation, constitutes a problem. While over distension of such vessel due to the application of excess fluid pressure is highly damaging the endothelium, prolonged collapse of the lumen, and the associated hemolysis and clotting which may be caused thereby must also be avoided.
Blood is a superior preserving solution (as compared to saline). However, to date, a method and device have not been disclosed wherein blood, utilized as a preservative for harvested vessels, might be effectively and efficiently directed through the lumen of harvested arteries and veins while, at the same time, maintaining a temperature close to that of normal body temperature and a flow mimicking the pulsatile flow and pressure ranges to which the vessel is normally exposed (pre-excision)